Early onset of alcohol use is associated with cognitive deficits and enhanced vulnerability to alcohol use disorder in adulthood. Individuals may be vulnerable to alcohol at this time because the frontal lobes are undergoing significant myelination throughout adolescence to enhance working memory and increase control of behaviors and emotions in adulthood. Myelination is a process in which oligodendrocytes wrap white fatty sheaths around axons of mature neurons to an optimal thickness that ensures high-speed propagation of electrical signals along an axon and enhances neural connectivity. Imaging studies suggest that heavy drinking may increase addiction risk and mental health vulnerability in adulthood by disrupting myelination during adolescent development. Alternatively, these relationships could be due to shared genetic predispositions rather than result from alcohol exposure. We have used a preclinical animal model of voluntary binge drinking to begin dissecting the causal nature of these relationships between alcohol and myelinated fiber tracks in the frontal lobes. Our findings indicate adolescent binge drinking induces prefrontal myelin loss and enhances drinking risk in adulthood. The current proposal combines powerful biochemical, neuroanatomical, and behavioral approaches to gain insight into how alcohol differentially affects prefrontal myeloarchitecture in males and females and empirically test the role of pubertal hormones in heightened vulnerability to alcohol during adolescent development. These studies should lead to a greater understanding of myelination and potentially reveal new therapeutic targets to combat alcohol use disorder.
The proposed research is expected to contribute a knowledge base regarding adolescent development of prefrontal white matter, sensitivity of these axons to alcohol, and the role myelin pathology plays in prefrontal function in males and females using a rodent model. This work will open a new direction of scientific investigation in the field of addiction and launch subsequent definitive studies to investigate the functional significance of myelinated fiber pattern changes for mental health.
| McDougall, Sean; Vargas Riad, Wanette; Silva-Gotay, Andrea et al. (2018) Myelination of Axons Corresponds with Faster Transmission Speed in the Prefrontal Cortex of Developing Male Rats. eNeuro 5: |
| Schreiber, Allyson L; Lu, Yi-Ling; Baynes, Brittni B et al. (2017) Corticotropin-releasing factor in ventromedial prefrontal cortex mediates avoidance of a traumatic stress-paired context. Neuropharmacology 113:323-330 |
